Characterization of the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease.
The factor VIII/von Willebrand factor (f.VIII/vWf) protein was purified from the plasma of a patient with von Willebrand's disease (vWd). The patient had all of the classic laboratory findings of vWd except for the ristocetin-induced platelet aggregation of his own platelet-rich plasma. The disease has been documented in three generations. Comparison of the purified normal and vWd f.VIIi/vWf protein revealed several abnormalities, including decreased concentration of f.VIII/vWf antigen; decreased specific vWf activity; absence of the larger molecular forms of the f.VIII/vWf protein; carbohydrate deficiencies affecting the sialic acid, penultimate galactose and N-acetylglucosamine moieties; and decreased binding of the f.VIII/vWf protein to its platelet receptor. These studies indicate the multiplicity of biochemical and functional abnormalities associated with the f.VIII/vWf protein in vWd. f.VIII/vWf protein to normal f.VIII/vWf protein that had been treated with 2-mercaptoethanol (2-ME) to reduce the multimer size and then treated with specific exoglycosidases to remove the sialic acid and penultimate galactose residues revealed similar biologic properties.
D000117:Acetylglucosamine / Q000172:deficiency; D000941:Antigens; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005169:Factor VIII / Q000276:immunology / Q000378:metabolism; D005690:Galactose / Q000172:deficiency; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012794:Sialic Acids / Q000172:deficiency; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism
D000941:Antigens; D012794:Sialic Acids; D014841:von Willebrand Factor; D005169:Factor VIII; D000117:Acetylglucosamine; D005690:Galactose